The goal of this research proposal is to determine the role of Muller glia and Notch signaling in zebrafish retinal regeneration. Muller cells are a type of radial glia in the retina. Our laboratory has demonstrated that adult fish can regenerate retinal neurons and that Muller glia are mitotically active following retinal damage. What remains unknown are the types of cells produced by proliferating Muller glia in response to retinal injury. Likewise, we do not know the molecular mechanisms responsible for regulating retinal regeneration and retinal stem cell proliferation in the adult zebrafish retina. One candidate is the Notch signaling pathway. Notch has been implicated in regeneration of other zebrafish tissues, suggesting Notch signaling is required for regeneration. We hypothesize that Muller glia function as neuronal stem cells and that Notch signaling is required for activation of the regenerative response. I plan to test this hypothesis by: (1) conducting lineage-tracing experiments to identify the progeny of Muller glia in response to injury; and (2) manipulating Notch signaling in regenerating retinas of adult zebrafish. Understanding the regenerative response of the adult zebrafish retina may bring researches closer to the goal of repairing the effects of retinal damage in people.